A Study Evaluating the Efficacy and Safety of Oral Etrasimod in the Treatment of Adult Participants With Moderately to Severely Active Crohn's Disease (CULTIVATE)

• ClinicalTrials.gov Identifier: NCT04173273
• Recruitment Status: Recruiting
• First Posted: November 21, 2019
• Last Update Posted: March 14, 2023
• Sponsor: Pfizer
• Collaborator: Arena is a wholly owned subsidiary of Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: November 20, 2019
• First Posted Date: November 21, 2019
• Last Update Posted Date: March 14, 2023
• Actual Study Start Date: January 13, 2020
• Estimated Primary Completion Date: July 9, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 16, 2023)

• Proportion of Participants with Endoscopic Response [Substudy A] [ Time Frame: Weeks 14 and 52 ]
• Proportion of Participants With Endoscopic Response [Substudy 1] [ Time Frame: Week 14 ]
• Proportion of Participants With Endoscopic Response [Substudy 2] [ Time Frame: Week 14 ]
• Proportion of Participants With Clinical Remission Crohn's Disease Activity Index (CDAI) [Substudy 2] [ Time Frame: Week 14 ]
• Proportion of Participants With Clinical Remission CDAI [Substudy 3] [ Time Frame: Week 52 ]
• Proportion of Participants With Endoscopic Response [Substudy 3] [ Time Frame: Week 52 ]

Original Primary Outcome Measures (submitted: November 20, 2019)

Proportion of Participants Who Achieve Endoscopic Response [ Time Frame: Week 14 ]

Endoscopic response is defined as ≥ 50% decrease from baseline in simple endoscopic score in Crohn's disease (SES-CD)

Current Secondary Outcome Measures (submitted: February 16, 2023)

• Proportion of Participants With Clinical Remission CDAI [Substudy A] [ Time Frame: Up to Week 66 ]
• Change From Baseline in Simple Endoscopic Score in Crohn's Disease (SES-CD) Score [Substudy A] [ Time Frame: Baseline to Week 66 ]
• Change From Baseline in CDAI Score [Substudy A] [ Time Frame: Baseline to Week 66 ]
• Proportion of Participants With Clinical Remission CDAI [Substudy 1] [ Time Frame: Week 14 ]
• Proportion of Participants with Clinical Remission Patient Reported Outcome 2 (PRO2) [Substudy 1] [ Time Frame: Week 14 ]
• Proportion of Participants With Clinical Remission Patient Reported Outcome 2 (PRO2) [Substudy 2] [ Time Frame: Week 14 ]
• Proportion of Participants With Clinical Response CDAI [Substudy 2] [ Time Frame: Week 14 ]
• Proportion of Participants With Endoscopic Response and Clinical Remission CDAI [Substudy 2] [ Time Frame: Week 14 ]
• Proportion of Participants With Endoscopic Remission [Substudy 2] [ Time Frame: Week 14 ]
• Change from baseline in CD-PRO/SS [Substudy 2] [ Time Frame: Week 14 ]
• Proportion of Participants With Clinical Remission CDAI Among Participants In Clinical Remission CDAI at Substudy 3 Baseline [Substudy 3] [ Time Frame: Week 52 ]
• Proportion of Participants With Endoscopic Response Among Participants in Endoscopic Response at Substudy 3 Baseline [Substudy 3] [ Time Frame: Week 52 ]
• Proportion of Participants With Corticosteroid-Free Clinical Remission CDAI Among Participants Receiving Corticosteroids at Substudy 3 Baseline [Substudy 3] [ Time Frame: Week 52 ]
• Proportion of Participants With Endoscopic Remission [Substudy 3] [ Time Frame: Week 52 ]
• Proportion of Participants With Clinical Remission PRO2 [Substudy 3] [ Time Frame: Week 52 ]
• Proportion of Participants with Clinical Response or Endoscopic Response [Substudy 3] [ Time Frame: Week 52 ]
• Proportion of Participants With Clinical Remission CDAI by Visit up to the End Of Treatment [Substudy 4] [ Time Frame: Up to Week 208 ]
• Proportion of Participants With Clinical Remission PRO2 by Visit up to the End Of Treatment [Substudy 4] [ Time Frame: Up to Week 208 ]
• Number and Severity of Adverse Events [ Time Frame: Up to approximately 70 weeks for Substudy A,approximately 24 weeks for Substudy 1 and 2; 42 weeks for Substudy 3; and 212 weeks for Substudy 4 ]
  Safety will be assessed by monitoring adverse events and clinically relevant changes in vital signs and clinical laboratory results.

Original Secondary Outcome Measures (submitted: November 20, 2019)

• Proportion of Participants Who Achieve Clinical Remission Worst Daily Abdominal Pain With Loose/Watery Stool Frequency Scores (APSF) [ Time Frame: Week 14 ]
  Clinical remission APSF is defined as unweighted average worst daily abdominal pain (AP) score ≤ 1 (using a 4-point scale; ie, 0 [none] to 3 [severe]) and unweighted average daily loose/watery (Bristol Stool Form Scale [BSFS] type 6 or 7) SF score ≤ 3.
• Number and Severity of Adverse Events [ Time Frame: Up to Week 66 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study Evaluating the Efficacy and Safety of Oral Etrasimod in the Treatment of Adult Participants With Moderately to Severely Active Crohn's Disease
• Official Title: A Multicenter, Randomized, Double-Blind, Parallel-Group Study to Assess the Efficacy and Safety of Oral Etrasimod as Induction and Maintenance Therapy for Moderately to Severely Active Crohn's Disease
• Brief Summary: This is a Phase 2/3 study that comprises 5 substudies designed to evaluate the efficacy, safety, and tolerability of oral etrasimod as therapy in adult participants with moderately to severely active Crohn's disease (CD) who are refractory or intolerant to at least 1 of the current therapies for CD (ie, corticosteroids, immunosuppressants, or biologics). The overall duration of this study is up to 282 weeks, inclusive of the Screening Period, Treatment Period of up to 274 weeks (Induction, Extension or Maintenance, and Long-term Extension Periods), and the 4-Week Follow-Up Period for safety assessment.

Detailed Description

This study includes 5 substudies:

Substudy A - Phase 2: A Phase 2, randomized, double-blind, substudy to assess the safety, tolerability, and efficacy of oral etrasimod therapy in participants with moderate to severe CD that supports the selection of an induction and maintenance dose(s) for Phase 3.

Substudy 1 - Phase 2: A Phase 2b randomized, double-blind, placebo-controlled, dose-ranging induction substudy to evaluate etrasimod as induction therapy and select an induction and maintenance dose(s) for continued evaluation in Phase 3.

Substudy 2 - Induction: A Phase 3 randomized, double-blind, placebo-controlled substudy to evaluate etrasimod as induction therapy.

Substudy 3 - Maintenance: A Phase 3 randomized, double-blind, placebo-controlled substudy to evaluate etrasimod as maintenance therapy. Participants from Substudy 1 and Substudy 2 will be enrolled in Substudy 3.

Substudy 4 - Long-Term Extension: A long-term extension substudy for participants who complete at least 52 weeks of treatment. Participants from Substudy 3 and Substudy A are planned to be enrolled in Substudy 4.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Crohn's Disease

Intervention

• Drug: Etrasimod
  Dose A taken by mouth, once daily.
  Other Name: APD334
• Drug: Etrasimod
  Dose B taken by mouth, once daily.
  Other Name: APD334
• Drug: Placebo
  Etrasimod matching placebo tablet taken by mouth, once daily.

Study Arms

• Experimental: Etrasimod Dose A
  Intervention: Drug: Etrasimod
• Experimental: Etrasimod Dose B
  Intervention: Drug: Etrasimod
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 16, 2023): 1115
• Original Estimated Enrollment (submitted: November 20, 2019): 225
• Estimated Study Completion Date: August 1, 2031
• Estimated Primary Completion Date: July 9, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Eligibility criteria applicable to all substudies:

Inclusion Criteria:

• Men or women 18 to 80 years of age,
• Ability to provide written informed consent or assent and to be compliant with the schedule of protocol assessments
• Diagnosed with Crohn's disease (CD) ≥ 3 months
• Have moderately to severely active CD at Screening

• Demonstrated inadequate response (ie, primary non-response), loss of response to, or intolerance to ≥ 1 of the following therapies for the treatment of CD:

  1. Oral corticosteroids (eg, prednisone or its equivalent, budesonide)
  2. Immunosuppressants (eg, azathioprine [AZA], 6 mercaptopurine [6-MP], or methotrexate [MTX])
  3. Tumor necrosis factor alpha (TNFα) antagonists (eg, infliximab, adalimumab, certolizumab pegol, or biosimilars)
  4. Integrin receptor antagonist (eg, vedolizumab)
  5. Interleukin -12/-23 antagonist (eg, ustekinumab)
• Females of childbearing potential must be nonpregnant
• Females of childbearing potential and males must use contraception

Exclusion Criteria:

• History of inadequate response (ie, primary non-response) to agents from ≥ 2 classes of biologics marketed for the treatment of CD (ie, TNFα antagonists, interleukin 12/ 23 antagonist, and integrin receptor antagonist).
• Have ulcerative colitis, indeterminate colitis, microscopic colitis, ischemic colitis, radiation colitis, diverticular disease associated colitis, toxic megacolon, or active infectious colitis or test positive for Clostridioides difficile toxin at Screening.
• Have functional or post-operative short-bowel syndrome or any associated complications that may require surgery or interfere with efficacy assessments
• Had surgical treatment for intra abdominal abscesses ≤ 8 weeks prior to randomization or surgical treatment for perianal abscesses ≤ 4 weeks prior to randomization.
• Had intestinal resection ≤ 24 weeks prior to randomization or other intra abdominal surgeries ≤ 12 weeks prior to randomization.
• Have an ileostomy or a colostomy.

Inclusion Criteria for Substudy 3:

- Participants who entered the Extended Induction Period of Substudy 1 and Substudy 2 must have completed the Extended Induction -Week 6 Visit

Inclusion Criteria for Substudy 4:

- Participant must have completed the Week 52 Visit of Substudy 3 or the Week 66 Visit of Substudy A

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Pfizer CT.gov Call Center; 1-800-718-1021; ClinicalTrials.gov_Inquiries@pfizer.com

• Listed Location Countries: Argentina, Australia, Austria, Belarus, Belgium, Bosnia and Herzegovina, Bulgaria, Canada, Chile, Colombia, Croatia, Czechia, Denmark, Egypt, France, Georgia, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Lebanon, Lithuania, Malaysia, Mexico, Moldova, Republic of, Netherlands, Norway, Philippines, Poland, Portugal, Puerto Rico, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Switzerland, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: India, Latvia

Administrative Information

• NCT Number: NCT04173273
• Other Study ID Numbers: APD334-202; C5041006 ( Other Identifier: Alias Study Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Arena Pharmaceuticals
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Arena Pharmaceuticals
• Collaborators: Arena is a wholly owned subsidiary of Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: March 2023